Effects of repeated antidepressant treatment on type 4A phosphodiesterase (PDE4A) in rat brain

In a previous study, an up-regulation of rolipram-sensitive, low-K-m, cycli c AMP phosphodiesterase (PDE4) subtype PDE4A in rat cerebral cortex followi ng repeated treatment of desipramine was observed. To determine whether thi s effect is shared by antidepressants from different pharmacological classe s, PDE4A expression was examined using immunoblot analyses following repeat ed treatment with the norepinephrine reuptake inhibitor desipramine, the mo noamine oxidase inhibitor phenelzine, the atypical antidepressant trazodone , and the serotonin reuptake inhibitor fluoxetine, Desipramine, phenelzine, and fluoxetine all increased the intensities of the PDE4A bands in hippoca mpal preparations; trazodone did not. In preparations of cerebral cortex, t he intensities of the PDE4A bands were increased following desipramine trea tment, not changed following phenelzine or fluoxetine treatment, and decrea sed following trazodone treatment. It appears that repeated treatment with antidepressant drugs from different pharmacological classes produces simila r effects on the expressions of PDE4A variants in hippocampus, This effect is not correlated with the changes in beta-adrenergic receptor densities, s uggesting these antidepressants may at some point alter intracellular signa l transduction pathways in a similar manner.